Abstract
Alzheimer’s disease (AD) is an incurable form of dementia affecting millions of people worldwide and costing billions of dollars in health care-related payments, making the discovery of a cure a top health, societal, and economic priority. Peptide-based drugs and immunotherapies targeting AD-associated beta-amyloid (Aβ) aggregation have been extensively explored; however, their therapeutic potential is limited by unfavorable pharmacokinetic (PK) properties. Peptoids (N-substituted glycine oligomers) are a promising class of peptidomimetics with highly tunable secondary structures and enhanced stabilities and membrane permeabilities. In this review, the biological activities, structures, and physicochemical properties for several amyloid-targeting peptoids will be described. In addition, metal-chelating peptoids with the potential to treat AD will be discussed since there are connections between the dysregulation of certain metals and the amyloid pathway.
Highlights
Alzheimer’s disease (AD) is an incurable form of dementia afflicting an estimated 5.5 millionAmericans [1]
This review presents the structures, methods biological activities, and physicochemical properties for various antiamyloidogenic peptoids.used, In addition, several metal-chelating peptoids are properties for various antiamyloidogenic peptoids
Emerging evidence suggests soluble aggregates rather fibrils are responsible for AD-associated neurotoxicity, which has led to a shift in approach in than fibrils are responsible for AD-associated neurotoxicity, which has led to a shift in approach in anti-amyloid drug drug design design [35,36]
Summary
Alzheimer’s disease (AD) is an incurable form of dementia afflicting an estimated 5.5 million. Challenges surrounding AD drug discovery include mis-diagnosis of clinical trial patients [10,11,12], a lack of reliable biomarkers [10], and an incomplete understanding of the complex and multifaceted disease pathology involving tau hyper-phosphorylation, Aβ aggregation, cholinergic dysfunction, metal dysregulation, inflammation, and oxidative stress [3,6,13,14], which are often interconnected. Peptoids (N-substituted glycine oligomers; [16]) have emerged as a promising class of peptidomimetics [17] with a range of properties, including anti-cancer [18] and antibacterial. This review presents the structures, methods biological activities, and physicochemical properties for various antiamyloidogenic peptoids.used, In addition, several metal-chelating peptoids are properties for various antiamyloidogenic peptoids. The medicinal of peptide and peptoid foldamers, of peptide andinteractions, peptoid foldamers, including antibacterial properties and The theirmedicinal abilities toproperties disrupt protein-protein have been reviewed [19,20]. Kodadek and Vanderstichele [31] and will not be discussed here
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